Reliable and robust

 

The most common form of dementia, AD affects 26 million people worldwide and is characterized by misfolded beta-amyloid and tau proteins. While the oligomeric forms of these proteins play a pivotal role in the patho-physiology of the disease, oligomer-specific research and development of therapeutics, biomarkers and diagnostics can be challenging because of the inherent instability of these protein aggregates.

 

Founded in 1997 by Drs. Hans-Ulrich Demuth and Konrad Glund, Probiodrug’s aim is to become a leading company in the development of Alzheimer’s treatments and to thereby provide a better life for patients. The company has identified a new therapeutic concept linked to disease initiation and progression—the development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight AD.

 

While most new drugs have focused on general Abeta formation or Abeta/plaque clearance, Probiodrug targets a specific type of Abeta—pGlu-Abeta, which is crucial in the formation of soluble, highly toxic “pre-plaques” called Abeta oligomers. Probiodrug is developing proprietary product candidates to target toxic pGlu-Abeta via two modes of action, by inhibiting the production of pGlu-Abeta and by clearing existing pGlu-Abeta from the brain. The company’s approaches comprise the development of specific inhibitors for the enzyme Glutaminyl Cyclase (QC), which is essential for the formation of pGlu-Abeta, and the development of a monoclonal antibody targeting pGlu-Abeta to enhance its clearance.

 

Crossbeta’s proprietary stabilization technology generates pure and functional preparations of oligomeric protein species and thereby overcomes this problem, enabling highly reproducible and well-controlled assays for preclinical and clinical R&D.

 

According to Inge Lues, chief development officer of Probiodrug, “The potential of Crossbeta’s unique technology has significant impact to overcome the challenge of establishing and validating sensitive and specific assays for Abeta- and pGlu-Abeta-oligomers to be used in the clinical studies of Probiodrug’s lead candidate, glutaminyl cyclase inhibitor PQ912.”

 

He added, “Crossbeta has specific technology for making stable and pure preparations of Aß oligomers, something that is unprecedented and which the Alzheimer’s field has been aiming to achieve for a long time. Through the partnership with Crossbeta, Probiodrug has gained access to these well-defined and stable preparations, thereby significantly increasing the chance of success of establishing reliable and robust Aß-related biomarker assays. These assays will support Probiodrug’s endeavors in the clinical development of therapeutic compound PQ912.”

 

Stabilizing oligomers and targeting toxic oligomers is the basis for Crossbeta’s oligomer drug discovery platforms, which are accessible for partnering in therapeutic areas such as Alzheimer’s, Parkinson’s, Huntington’s and type 2 diabetes. Its Alzheimer’s program has recently completed a high-throughput screening campaign with 100,000 compounds, resulting in the selection of five hit classes with more than 50-percent neutralizing effect on oligomer-induced neurotoxicity. Stable oligomers can also be used as reference in biomarker assays.

 

Crossbeta will use its proprietary technology to generate and supply stable oligomers of different Aß species of interest, such as Aß1-42 and pGluAß3-42, both implicated in Alzheimer’s disease. These oligomers will be implemented by Probiodrug in its innovative biomarker assay development and application in clinical research and development.

 

“This strategic partnership with Probiodrug is an important recognition of our expertise and capabilities,” said Guus Scheefhals, CEO of Crossbeta. “As a clinical-stage company, Probiodrug is a particularly important partner in our growing collaborative network. We look forward to contributing towards the development of this promising therapeutic approach targeting AD.”